LIONS (PLK4 Inhibitor in Advanced Solid Tumors)
- Conditions
- Advanced Solid Tumor
- Registration Number
- NCT06232408
- Lead Sponsor
- Repare Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 80
Inclusion Criteria:<br><br> - Written informed consent or assent, according to local guidelines, signed and dated<br> by the patient or legal guardian prior to the performance of any study-specific<br> procedures, sampling, or analyses.<br><br> - Male or female and = 12 years-of-age at the time of signature of the consent or<br> assent, and are at least 6th grade reading level to consent; participants < 18 years<br> of age must weigh at least 40 kg.<br><br> - Life expectancy = 4 months.<br><br> - Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.<br><br> - Locally advanced or metastatic solid tumor that has progressed or was nonresponsive<br> or intolerant to available therapies and for which no standard or available curative<br> therapy exists.<br><br> - Measurable disease as per RECIST v1.1 or INRC.<br><br> - Existing biomarker profile (tumor tissue or plasma) reported from a local test<br> obtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumor<br> biomarkers.<br><br> - Available tumor tissue.<br><br> - Molecularly eligible tumor profile from a CLIA-certified pathology report.<br><br> - Ability to comply with the protocol and study procedures detailed in the Schedule of<br> Assessments.<br><br> - Ability to swallow and retain oral medications.<br><br> - Acceptable organ function at screening.<br><br> - Acceptable blood counts at screening.<br><br> - Negative pregnancy test (serum or urine) for females of childbearing potential at<br> Screening and while on study drug.<br><br> - Resolution of all toxicities of prior treatment or surgery.<br><br> - Use of highly effective forms of contraception.<br><br>Exclusion Criteria:<br><br> - History or current condition (such as transfusion dependent anemia or<br> thrombocytopenia), therapy, or laboratory abnormality that might confound the study<br> results, or interfere with the patient's participation for the full duration of the<br> study treatment.<br><br> - Life-threatening illness, medical condition, active uncontrolled infection, or organ<br> system dysfunction or other reasons which, in the investigator's opinion, could<br> compromise the patient's safety.<br><br> - Uncontrolled, symptomatic brain metastases.<br><br> - Presence of other known second malignancy with the exception of any cancer that has<br> been in complete remission for = 2 years or completely resected squamous and basal<br> cell carcinomas of the skin.<br><br> - Patients with active, uncontrolled bacterial, fungal, or viral infection, including<br> hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus<br> (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.<br><br> - Clinically significant vascular (both arterial and venous) and non-vascular cardiac<br> conditions, active or within 6 months prior to enrollment.<br><br> - Moderate or severe hepatic impairment (ie, Child-Pugh class B or C).<br><br> - Uncontrolled high blood pressure.<br><br> - Chemotherapy, small molecule or biologic antineoplastic agent given within 21 days.<br><br> - Previously prescribed receptor activator of nuclear factor kappa B ligand (RANKL)<br> inhibitor initiated less than 4 months prior to trial entry. Bisphosphonates are<br> allowed if initiated/administered at least 28 days prior to enrollment.<br><br> - I-131 Meta-Iodo-Benzyl-Guanidine (MIGB) therapy within 6 weeks prior to initiation<br> of trial treatment.<br><br> - Prior treatment with a PLK4 inhibitor.<br><br> - Current treatment with medications that are known to prolong the QT interval.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed per NCI CTCAE v5.0 criteria;Dose Limiting Toxicities to determine a maximum tolerated dose and schedule of RP-1664 based on safety and tolerability as measured by CTCAE v5.0, pharmacokinetic parameters, pharmacodynamic readouts and efficacy data per RECIST or INRC criteria
- Secondary Outcome Measures
Name Time Method To assess the PK parameters of RP-1664 in the fed and fasted states by measurement of plasma concentrations of RP-1664 with calculation of maximum observed plasma concentration (Cmax).;To assess the preliminary anti-tumor activity of RP-1664 in participants with molecularly selected advanced solid tumors treated at pharmacologically active dose ranges. Anti-tumor activity will be measured by ORR according to RECIST 1.1 and INRC.